Swab-Seq: A high-throughput platform for massively scaled up SARS-CoV-2 testing
Joshua S. Bloom,
Eric M Jones,
Nathan B. Lubock,
A. Sina Booeshaghi,
Oliver F. Brandenberg,
Scott W. Simpkins,
Bianca Judy Choe,
Evann E. Hilt,
Manish J. Butte,
Aaron R. Cooper,
Omai B. Garner,
Valerie A. Arboleda
Posted 06 Aug 2020
medRxiv DOI: 10.1101/2020.08.04.20167874
Posted 06 Aug 2020
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is due to the high rates of transmission by individuals who are asymptomatic at the time of transmission. Frequent, widespread testing of the asymptomatic population for SARS-CoV-2 is essential to suppress viral transmission and is a key element in safely reopening society. Despite increases in testing capacity, multiple challenges remain in deploying traditional reverse transcription and quantitative PCR (RT-qPCR) tests at the scale required for population screening of asymptomatic individuals. We have developed SwabSeq, a high-throughput testing platform for SARS-CoV-2 that uses next-generation sequencing as a readout. SwabSeq employs sample-specific molecular barcodes to enable thousands of samples to be combined and simultaneously analyzed for the presence or absence of SARS-CoV-2 in a single run. Importantly, SwabSeq incorporates an in vitro RNA standard that mimics the viral amplicon, but can be distinguished by sequencing. This standard allows for end-point rather than quantitative PCR, improves quantitation, reduces requirements for automation and sample-to-sample normalization, enables purification-free detection, and gives better ability to call true negatives. We show that SwabSeq can test nasal and oral specimens for SARS-CoV-2 with or without RNA extraction while maintaining analytical sensitivity better than or comparable to that of fluorescence-based RT-qPCR tests. SwabSeq is simple, sensitive, flexible, rapidly scalable, inexpensive enough to test widely and frequently, and can provide a turn around time of 12 to 24 hours.
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